Ischemic heart disease typically results from an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Progressive atherosclerosis with increasing occlusion of coronary arteries leads to a reduction in coronary blood flow. Atherosclerosis is a type of arteriosclerosis in which cells including smooth muscle cells and macrophages, fatty substances, cholesterol, cellular waste product, calcium and fibrin build up in the inner lining of a body vessel. Arteriosclerosis is thickening and hardening of arteries. Blood flow can be further decreased by additional events such as changes in circulation that lead to hypoperfusion, vasospasm or thrombosis.
Myocardial infarction (MI) is one form of heart disease that often results from the sudden lack of supply of oxygen and other nutrients. The lack of blood supply is a result of a closure of the coronary artery (or any other artery feeding the heart) which nourishes a particular part of the heart muscle. The cause of this event is generally attributed to arteriosclerosis in coronary vessels.
Formerly, it was believed that an MI was caused by a slow progression of closure from, for example, 95% then to 100%. However, an MI can also be a result of initially minor blockages where, for example, there is a rupture of a cholesterol plaque, subsequent formation of blood clots in the artery resulting in blockage of the flow of blood and eventual downstream cellular damage. This damage can cause irregular rhythms that can be fatal, even though the remaining muscle is strong enough to pump a sufficient amount of blood. As a result of this insult to the heart tissue, scar tissue tends to naturally form.
Various procedures, including mechanical and medicinal, are known for reopening blocked arteries. An example of a mechanical procedure is balloon angioplasty with stenting, while an example of a medicinal treatment is the administration of a thrombolytic agent, such as urokinase. Such procedures do not, however, treat actual tissue damage to the heart. Other systemic drugs, such as ACE-inhibitors and beta-blockers, may be effective in reducing cardiac load post-MI, although a significant portion of the population that experiences a major MI ultimately develop heart failure.
An important component in the progression to heart failure is post-MI remodeling of the heart due to mismatched mechanical forces between the infarct region and the healthy tissue resulting in uneven stress distribution in the wall of the left ventricle. The principle components of remodeling include myocyte death, edema and inflammation, followed by fibroblast infiltration and collagen deposition, and finally scar formation. The main component of the scar is collagen. Since mature myocytes of an adult are not regenerated, the infarct region experiences significant thinning. Myocyte loss is the major etiologic factor of wall thinning and chamber dilation that may ultimately lead to cardiomyopathy. Further, remote regions of the heart may experience hypertrophy (thickening) resulting in an overall enlargement of the left ventricle. These changes in the heart often result in changes in a patient's lifestyle, e.g., the ability to walk and to exercise. These changes also correlate with physiological changes that result in increase in blood pressure and worsening systolic and diastolic performance.
Another means of treating post-MI complications such as cardiomyopathy is dynamic cardiomyoplasty wherein a patient's latissimus dorsi muscle is wrapped around the ventricles and electostimulated in synchrony with the contractions of the heart by means of an implanted cardio-myostimulator. A relatively recent modification of dynamic cardiomyoplasty is cellular cardiomyoplasty in which individual cells are delivered to the damaged myocardium where they integrate into the myocardial tissue proliferate and eventually provide an improvement in contractile force. The cells may be, without limitation, fetal or embryonic cardiomyocytes, adult cardiomyocytes, skeletal myoblasts, smooth muscle cells, bone marrow derived stromal cells, undifferentiated blood cells and the like. The problem is delivering the cells to the damaged myocardium and retaining them there in a fully operative condition until the cells have had the opportunity to achieve their therapeutic effect either by secretion of a plethora of cytokinies, or by integrating into the heart tissue and or/by trans-differentiating into cardiomyocytes.
What is needed, then, is a method of delivering cells to the damaged myocardium and retaining the cells at the myocardial locus in their native fully potent state until they have had the opportunity to exert their therapeutic benefit. The current invention provides such a method and a composition to use with the method.